Anti-atherogenicity in women does not prevent restenosis after balloon angioplasty.

To test the hypothesis that anti-atherogenicity in women exerts beneficial effects to prevent restenosis formation after coronary angioplasty, we studied 493 men (988 lesions) and 81 women (159 lesions), aged 40-60 years, who had undergone successful balloon angioplasty and had follow-up angiography, 4.9 +/- 4.1 months later. We compared the extent of restenosis between men and women, and between pre- and post-menopausal women, which was assessed by a categorical definition of restenosis (more than 50% diameter stenosis at follow-up) and by percent diameter measured immediately after angioplasty and at follow-up. Hypertension was more frequent in women and a significantly lower percentage of women smoked. In women, the levels of total cholesterol and low-density lipoprotein cholesterol were higher. The location of dilated lesions, frequency of angioplasty for lesions with chronic total occlusion, and frequency of emergency angioplasty in patients with unstable angina or acute myocardial infarction were similar in men and women. Restenosis formation, estimated by the categorical definition or percent diameter, did not differ between men and women, or between pre- and post-menopausal women. Menopausal status or sex was not an independent predictor of restenosis by multivariate analysis. Thus, the benefit of anti-atherogenicity in women does not play an important role in preventing restenosis after coronary angioplasty.

Coronary angioplasty ameliorates hypoperfusion-induced endothelial dysfunction in patients with stable angina pectoris.

OBJECTIVES: This study sought to investigate the effect of coronary angioplasty on chronic hypoperfusion-induced endothelial dysfunction in patients with coronary heart disease. BACKGROUND: The endothelium is an important component for organ flow regulation. Ischemia with or without reperfusion is known to cause endothelial dysfunction. We tested the hypothesis that chronic hypoperfusion impairs endothelial function in the angiographically normal coronary artery segment distal to stenosis and that the impairment by chronic hypoperfusion is reduced by coronary angioplasty. METHODS: In 13 patients with stable angina pectoris, substance P (10, 30 and 100 pmol) and nitroglycerin (200 micrograms) were sequentially infused into the coronary artery in a cumulative manner on the day after coronary angioplasty. In 10 of these patients, vascular responses to these agents were again investigated 3 months after angioplasty. Changes in vascular diameter were evaluated in vessels located proximal and distal to the target lesion, both of which were angiographically normal, by performing computer-assisted quantitative coronary angiography. In five patients, the transstenotic pressure gradient was also measured with a pressure sensor-mounted guide wire before angioplasty. RESULTS: On the day after angioplasty, the magnitude of dilation by substance P in distal segments was significantly less than that in proximal segments and inversely correlated with the transstenotic pressure gradient (p < 0.05) and lesion stenosis (p < 0.05). There was no difference in nitroglycerin-induced vasodilation between the two vessel segment groups. Three months later, the impaired response to substance P in the distal segment was restored to normal. CONCLUSIONS: We conclude that chronic hypoperfusion impairs endothelium-dependent dilation of coronary artery distal to critical stenosis in patients with ischemic heart disease and that coronary angioplasty ameliorates the endothelial dysfunction within 3 months.

Effects of arterial distensibility on left ventricular ejection in the depressed contractile state.

OBJECTIVE: The aim was to evaluate the effects of arterial distensibility on ventricular ejection in various ventricular contractile states: (1) control; (2) a regionally depressed contractile state due to left circumflex coronary artery occlusion (ligation); (3) a globally depressed contractile state induced by lignocaine (lignocaine); and (4) a globally augmented contractile state due to dobutamine infusion (dobutamine). METHODS: Arterial compliance was decreased from 2.3 x 10(-4) dyne-1.cm5 (C2.3) to 0.4 x 10(-4) dyne-1.cm5 (C0.4), maintaining other afterload components and left ventricular end diastolic pressure constant. Nine excised perfused and paced canine hearts, supported from donor dogs, were used. RESULTS: In control, ligation, lignocaine, and dobutamine groups, the difference in cardiac output between the compliance values of C0.4 and C2.3 was 124(SEM 32), 204(36), 163(33), and 130(24) ml, respectively. Thus cardiac output at C0.4, as a percentage of that at C2.3, was 88(2.8)% (control), 75(2.9)% (ligation), 82(2.9)% (lignocaine), and 88(2.4)% (dobutamine), respectively: control v ligation, and lignocaine v ligation, p < 0.001; control v lignocaine, and dobutamine v ligation, p < 0.01. Stroke work at C0.4 decreased in the ligation group (63%, p < 0.001) and in the lignocaine group (70%, p < 0.001). CONCLUSIONS: When cardiac dysfunction is already present, decreased arterial distensibility has a further deleterious effect on cardiac output. This may be due to the fact that the pressure at the end of ejection is higher and as a result the change in dimension during ejection is considerably reduced, especially in cases with depressed cardiac function caused by afterload dependency.

Effects of afterload elevation on the ischemic myocardium in isolated, paced canine heart with partial coronary stenosis.

The effect of afterload elevation on the ischemic myocardium was examined in an isolated, paced canine heart with a partial coronary stenosis. The coronary blood flow of the left circumflex coronary artery was reduced to approximately one-third of the values before stenosis. The left circumflex coronary stenosis produced a decrease in global ventricular function, a decrease in systolic shortening and deviation of the ST-segment of the epicardial electrocardiogram and an increase in myocardial carbon dioxide (CO2) tension of the ischemic region. Then, afterload elevation with constant preload decreased the myocardial CO2 tension and improved the ST-segment deviation of the ischemic myocardium. Mechanical function, estimated by the relation between mean aortic pressure and systolic shortening, also improved with elevation of mean aortic pressure. In contrast, afterload elevation combined with preload elevation did not improve ischemic injury, as estimated by myocardial CO2 tension, and did not improve ST-segment deviation or mechanical function despite an increase in left circumflex coronary flow. These results suggest that the elevation of afterload pressure under constant preload improves ischemia produced by a partial coronary stenosis due to increased coronary blood supply; however, the preload elevation counterbalances the beneficial effects of afterload elevation.

Load dependency of end-systolic pressure-volume relations in isolated, ejecting canine hearts.

If characteristic muscle properties such as myocardial viscosity and/or shortening deactivation influence left ventricular ejection in the whole heart, the slope of the left ventricular end-systolic pressure-volume relation should be a function of both the contractile state and the loading mode. Thus, the load dependence of the end-systolic pressure-volume relation was examined using isolated, perfused canine hearts ejecting saline into a hydraulic loading system. The instantaneous left ventricular volume was measured with a plethysmograph. Under constant coronary flow and heart rate, two regression lines for end-systolic pressure-volume relations in two sets of loading modes were obtained: (1) Preload (left ventricular end-diastolic pressure; 4-15 mmHg) changes under fixed afterload impedance (preload changes); (2) Afterload impedance (peripheral resistance; 1.9-9.6 x 10(3) dyn sec cm-5) changes under fixed left ventricular end-diastolic volume (afterload changes). The slope of the end-systolic pressure-volume relation with afterload changes was steeper than that with preload changes (6.3 +/- 0.7 vs 4.8 +/- 0.6 mmHg/ml, p less than 0.05). Accordingly, under constant coronary flow, the slope of the end-systolic pressure-volume relation depended on loading conditions within the physiological range of afterload impedance and preload. This finding supports our hypothesis and implies that the slope change is of limited value as a contractile index in the ejecting heart.

Effects of changes in afterload impedance on left ventricular ejection in isolated canine hearts: dissociation of end ejection from end systole.

To examine how end systole differs from end ejection and also whether the slope of the end systolic pressure-volume relation can be approximated to that of the end ejection pressure-volume relation, nine isolated, perfused, paced canine hearts ejecting into a hydraulic loading system that simulated the aortic input impedance of a dog's arterial tree were studied. To measure left ventricular volume changes the heart was placed in a plethysmograph. Peripheral resistance (Rp) and arterial compliance (C) were independently varied from 1.9 (Rp = 1.9) to 3.3, 6.4, and 9.6 X 10(8) Pa.m-3.s (Rp run) with a constant value of compliance 1.3 X 10(-9) Pa-1.m3 (C = 1.3), and from C = 0.4 to C = 0.8, C = 1.3 and C = 2.3 (C run) with a constant value of resistance (Rp = 6.4). Five pressure-volume loops were obtained by changing the end diastolic volume at each value of compliance and peripheral resistance. It was clearly shown that ventricular ejection continued after end systole and the time duration between end systole and end ejection became longer with increasing arterial compliance (24(4) at C = 0.4 vs 49(4) ms at C = 2.3, p less than 0.001), while the time duration between end diastole and end systole was constant regardless of afterload impedance change. Regarding the left ventricular pressure-volume relation the end systolic relation was almost linear (r greater than or equal to 0.98) and the slope was not significantly affected by change in any afterload impedance tested. End ejection pressure-volume relation was also linear (r greater than or equal to 0.97) and the slopes in the peripheral resistance and compliance runs were lower than those of the end systolic pressure-volume relation in each corresponding run. The former slopes decreased at smaller values of Rp or larger values of C--namely, 4.4(0.6) at Rp = 9.6 vs 3.6(0.6) at Rp = 1.9, p less than 0.05; 4.8(0.6) at C = 0.4 vs 3.1(0.5) mmHg.ml-1 at C = 2.3, p less than 0.001. Thus it is concluded that end ejection is usually different from end systole and the time difference between them is affected by changes in arterial compliance. In addition, the slope of end ejection pressure-volume relation was dependent on the changes in afterload impedance and cannot be approximated to that of the end systolic pressure-volume relation.

Effects of preload alteration on the degree of ischemia and function of ischemic myocardium under constant mean aortic pressure, coronary perfusion pressure and heart rate in isolated perfused canine heart.

We examined the effects of preload alteration on global and regional (i.e., non-ischemic and ischemic areas) function in the presence of regional myocardial ischemia and on the degree of ischemia using 18 isolated, metabolically supported canine left ventricles. For this purpose, cardiac output (CO), systolic segment length change (SL), myocardial CO2 tension (PmCO2) and ST level of epicardial ECG were measured at 3 levels of left ventricular end-diastolic pressure (LVEDP), i.e., approximately 7 (low LVEDP), 11 (middle LVEDP), and 16 mmHg (high LVEDP) without and with left circumflex artery (LCx) stenosis under a constant mean aortic pressure (90 mmHg), mean coronary perfusion pressure (90 mmHg) and heart rate. In the Pre-ischemic stage, CO and SL increased significantly when LVEDP was elevated in a stepwise fashion by changing the height of the reservoir connected to the left atrium. There were no significant changes in PmCO2 or ST level. On the other hand, with LCx stenosis, CO did not show a subsequent increase at higher LVEDPs (i.e., from 796 +/- 103 ml/min at middle LVEDP to 931 +/- 153 ml/min at high LVEDP). Furthermore, there was no significant SL response in the LCx area following alterations of LVEDP, although there was considerable lengthening of end-diastolic length. Both increased PmCO2 and ST level of the LCx area, following LCx stenosis, further increased significantly with elevation of LVEDP. These results suggest the possibility that considerable elevation of LVEDP worsens the degree of ischemia and does not significantly augment ischemic regional myocardial function or global function, while mild elevation of preload improves or tends to improve simultaneously regional ischemic and global functions without aggravating the ischemic injury significantly. Therefore, we conclude that the preload level is quite important in managing ischemia induced myocardial dysfunction.

Effects of OPC-8212, a new positive inotropic agent, and dobutamine on left ventricular global and ischemic regional functions and coronary hemodynamics under coronary artery stenosis.

We have investigated the effects of OPC-8212, a new positive inotropic agent, and dobutamine, a known cardioselective inotropic agent, on global left ventricular (LV) and ischemic regional functions in 14 excised canine hearts with a flow-limiting stenosis of the left circumflex coronary artery (LCX) (i.e., 20-25% of control flow). OPC-8212 infusion (n = 7) under LCX stenosis improved cardiac depression [i.e., peak LV dP/dt increased from 1,295 +/- 143 mm Hg/s to 2,669 +/- 266 mm Hg/s (mean +/- SEM) (p less than 0.001)], while myocardial ischemic injury, assessed by myocardial CO2-tension and electrocardiogram (ECG)-ST changes, improved (i.e., delta CO2-tension and ECG-ST deviation decreased from 21.1 +/- 3.6 mm Hg and 3.8 +/- 0.6 mV to 13.3 +/- 2.8 mm Hg (p less than 0.01) and 2.0 +/- 0.7 mV (p less than 0.05), respectively). On the other hand, dobutamine infusion (n = 7) further increased myocardial CO2-tension and ECG-ST deviation [i.e., delta CO2-tension and ECG-ST deviation increased from 14.4 +/- 4.2 mm Hg and 2.5 +/- 1.2 mV to 29.0 +/- 6.0 mm Hg (p less than 0.01) and 4.9 +/- 1.0 mV (p less than 0.01), respectively]. At the same time, peak LV dP/dt clearly improved, but to a lesser degree; from 1,425 +/- 153 mm Hg/s to 2,393 +/- 245 mm Hg/s (p less than 0.001). There was also an increase in percent systolic segment shortening of each corresponding area as with OPC-8212.(ABSTRACT TRUNCATED AT 250 WORDS)

A new indirect method for measurement of sinoatrial conduction time and sinus node return cycle.

We developed a new indirect method for the measurement of sinoatrial conduction time (SACT) and the sinus node return cycle (SRC) with a transvenous catheter technique. Two early premature stimuli, at intervals 50 msec longer than the effective refractory period (ERP), were given to the right atrium. These early stimuli were followed by eight constant stimuli. The interval of the constant stimuli was a little shorter than the basic cycle length (BCL). The return cycle A1Ar was measured and plotted on the abscissa; the next interval ArA3, was measured and plotted on the ordinate. This was called the "base point". A new stimulus, A2, was then added to the train of stimulations, first at a point simultaneous with Ar. It was then shifted toward the last constant stimulus at 10-20 msec intervals until A2 met the ERP. The relationship between A1A2 and A2A3 was obtained by the repetition of the procedures with various A1A2 intervals. It had two zones, compensatory and non-compensatory. We postulate that the atriosinus conduction time of the last of the eight stimuli was equal to that of A2 when the stimulus A2 first captured and reset the sinus nodal pacemaker cells, as indicated by the transition point of the two zones. Based on this supposition, SACT and SRC could be measured as the intervals from the base point to the transition point and from the transition point to the eighth stimulus, respectively.

Responses of left ventricle to changes in aortic input impedance.

In order to evaluate how pressure and flow at the outlet of a ventricle are determined by the interaction between the ventricle and an aortic input impedance, we examined the effects of independent changes in the peripheral resistance and in the aortic compliance using isolated canine left ventricle preparations. There was an inverse linear relationship of mean values between pressure and cardiac output under pure resistance changes when coronary flow was maintained constant. But, when the coronary perfusion pressure depended on mean aortic pressure, the relationship was no longer linear under a critical aortic pressure. When aortic compliance was increased, late systolic flow was enhanced and late systolic pressure decreased such that the stroke volume increased. The top part of the pressure-volume loop showed a configurational change from the right side down to the left side down. Changes in pressure and flow wave forms, and in the pressure-volume loop can be predicted by an electrical model in which time varying capacitance arranged in series with the internal resistance was used as a ventricular model.